Dansyl C‐Glucoside as a Novel Agent Against Endotoxic Shock

Abstract

An efficient protocol to synthesize iodohydrins from alkenes is presented. Reactions were conducted in aqueous media using safe and readily available sodium iodide (the most abundant form of the element), and a highly convenient oxidant such as hydrogen peroxide. Addition of a protic acid triggers a faster and efficient process, a role formally related to that played by haloperoxidase enzymes in naturally occurring transformations. The successful application of these conditions to multigram scale preparations and over natural products derivatives is also discussed.

Sodium glucose cotransporter 1 ligand BLF501 as a novel tool for management of gastrointestinal mucositis

“…It is noteworthy that the dose of BLF501 necessary to protect from DXR-induced injury was much lower than doses of D-glucose or 3-OMG shown to protect from LPS-induced injury (25 μg/kg vs 2.5 g/kg). The ability of BLF501 to protect at low doses may reflect its high affinity for SGLT-1, a possibility supported by our previous in vitro finding that both D-glucose and BLF501 block LPS-induced release of IL-8, yet BLF501 is active at doses ~106-fold lower than that of D-glucose [21]. …”

“…This protective effect is independent of glucose metabolism, since BLF501 is a C-glycoside and, as such, does not enter the metabolic pathways of D-glucose [21]. The protective effect of the orally-administered SGLT-1 agonist 3-O-methyl-glucose (3-OMG), a non-metabolizable analog of D-glucose that does not enter glucose metabolic pathways, and of D-glucose has been previously reported in a model of LPS-induced injury to the intestinal mucosa [19].…”

“…The synthesis and a preliminary profiling of BLF501 have been described [21]. BLF501 resembles the structure (isosteric) of the natural O-glycoside, but cannot be metabolized (C-glycosides are unable to undergo glycolysis).…”

“…Based on these data, we speculated that SGLT-1-mediated signaling might be beneficial in maintaining intestinal mucosal integrity from chemotherapy-induced damage. To test this hypothesis, we examined the effects of BLF501 (formerly called “compound 5”), a synthetic compound which binds to SGLT-1 withdrawal [21], in a mouse model of doxorubicin (DXR)- and 5-fluorouracil (5-FU)-induced intestinal injury. Here, we show that BLF501-induced SGLT-1 activation protects against DXR- and 5-FU-induced injury by promoting proliferation of enterocytes and correct formation of tight and adherens junctions.…”

Disaccharide‐Based Anionic Amphiphiles as Potent Inhibitors of Lipopolysaccharide‐Induced Inflammation

“…[31,32] Several innovative molecules with no similarity to Lipid Ah ave been proposed as candidates for blocking LPStriggered pro-inflammatory signaling. [33][34][35] Still, no universal therapeutic remedy has been developed so far,a nd sepsis remains the leading causeo fd eath in intensive care units with up to 50 %m ortality rate. [36] Sepsis is progressivelyb elieved to represent the ultimate general cause of mortality from infection.…”